DESCRIPITON: (Applicant's abstract) Nitric oxide (NO) and peroxynitrite are reactive, short-lived species that are important mediators of various forms of inflammation. Recent studies have implicated the crucial role of NO and peroxynitrite in the pathogenesis of various forms of neurodegenerative disorders, including Parkinson's disease. Inotek Corporation is developing a unique NO scavenger, carboxy-PTIO, which, according to preliminary data, produces dramatic benefits in a variety of stringent inflammatory models, including experimental autoimmune encephalomyelitis and endotoxic shock. This class is exemplified by 2-phenyl-4,4,5,5-tetramethyl-imidazolineoxyl-1-oxyl-3-oxide (PTIO) and its water-soluble derivative, carboxy-PTIP (c-PTIO). Carboxy-PTIO scavenges excessive NO production and, in so doing, prevents the formation of toxic quantities of peroxynitrite, a reactive oxidant which causes cell dysfunction and organ failure. Carboxy-PTIO also has a direct protent scavenging effect on peroxynitrite. The specific aim of the present proposal is to perform definitive in vivo studies in murine model of Parkinson's disease in order to test whether carboxy-PTIO can be developed for the experimental therapy of this condition. The results of the present application will permit application of Phase 2 SBIR funding to support: pre-clinical pharmaceutical testing (advanced toxicity determinations, pathology, stability, pharmacokinetics, in vivo efficacy), investigational drug application to the FDA, and a Phase 1 clinical trial. PROPOSED COMMERCIAL APPLICATION: The domestic market for a novel, effective therapy for Parkinson's disease is conservatively estimated at $50 million per annum. Global markets are estimated at $150 million. Funding of SBIR Phases I and II will allow for market entry in 3.5 years.